Rotaxane-Based Molecular Machines for Organic Synthesis

UoM administered thesis: Phd

  • Authors:
  • Malcolm Gall


Within living organisms in the natural world, highly complex systems have evolved over billions of years to carry out the specific synthetic functions required to support and propagate life. Nature's use of biological machines for the synthesis of functional molecules has inspired synthetic chemists from a broad range of specialisms to design artificial molecular machines and systems capable of facilitating non-trivial synthetic tasks. A core strategy employed in attempting to emulate biological machines for synthesis has been to mimic Nature's ability to compartmentalise discrete aspects of a synthetic process. Rotaxanes are favourable architectures around which to design molecular machines as their mechanically-interlocked nature provides the chemist with a unique means by which to achieve compartmentalisation and to control the effective molarity of non-covalently linked components. The research presented in this thesis investigates the design, synthesis and operation of novel, rotaxane-based molecular machines for the non-trivial assembly of individual amino acid building blocks into information-rich oligopeptides. The artificial devices described herein each endeavour to emulate (in a primitive manner) one of Nature's most remarkable machines for synthesis: the ribosome. Information is programmed into these 'synthetic ribosomes' through their careful design and modular assembly; upon operation of the artificial molecular machine, this transcribed information is translated into a pre-defined oligopeptide product. The research presented in this thesis is laid out as follows:Chapter 1 reviews the current state of the art in biomimetic molecular machines and systems capable of promoting non-trivial synthetic tasks;Chapter 2 describes a molecular machine capable of non-proteinogenic oligopeptide synthesis via the sequence-specific assembly of beta-homo amino acid building blocks;Chapter 3 presents a device which operates upon a polymer to assemble individual leucine units into a homo-oligopeptide. This product forms a secondary alpha-helical structure capable of asymmetric organocatalysis in the Juliá-Colonna epoxidation of chalcone derivatives;Chapter 4 details a novel mode of amide-bond-forming catalysis for rotaxane-based molecular machines with a view to assembling an advanced peptidic precursor to Penicillin G.Chapters 2 and 3 are presented as manuscripts which have been compiled for peer-review publication and which represent the collaborative efforts of the Author and the researchers indicated at the beginning of each chapter. The Author's contributions are also outlined at the beginning of each chapter. These manuscripts have been modified only to ensure consistency with the other chapters contained in this thesis.


Original languageEnglish
Awarding Institution
Award date1 Aug 2017